ES2846772T3 - Derivados de pentaciclotienil e indanil urea como abridores de canales de potasio - Google Patents

Derivados de pentaciclotienil e indanil urea como abridores de canales de potasio Download PDF

Info

Publication number: ES2846772T3
Authority: ES; Spain
Prior art keywords: compounds; dihydro; methylurea; difluorophenyl; compound
Prior art date: 2017-02-28
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES19179900T

Other languages

English (en)

Spanish (es)

Inventor

Michael Bös

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

ACOUSIA THERAPEUTICS GmbH

Original Assignee

ACOUSIA THERAPEUTICS GmbH

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2017-02-28

Filing date

2018-02-27

Publication date

2021-07-29

2018-02-27 Application filed by ACOUSIA THERAPEUTICS GmbH filed Critical ACOUSIA THERAPEUTICS GmbH

2021-07-29 Application granted granted Critical

2021-07-29 Publication of ES2846772T3 publication Critical patent/ES2846772T3/es

Status Active legal-status Critical Current

2038-02-27 Anticipated expiration legal-status Critical

Links

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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
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- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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- A61P27/16—Otologicals
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- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/26—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of rings other than six-membered aromatic rings
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/40—Y being a hydrogen or a carbon atom
- C—CHEMISTRY; METALLURGY
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/43—Y being a hetero atom
- C07C323/44—X or Y being nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/63—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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Public Health (AREA)
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Animal Behavior & Ethology (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Plural Heterocyclic Compounds (AREA)
Cosmetics (AREA)
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ES19179900T 2017-02-28 2018-02-27 Derivados de pentaciclotienil e indanil urea como abridores de canales de potasio Active ES2846772T3 (es)

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EP17158326.3A EP3366683A1 (fr)	2017-02-28	2017-02-28	Amides, acetamides et ureas cycliques pour ouvris les voies de calcium

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ES19179900T Active ES2846772T3 (es)	2017-02-28	2018-02-27	Derivados de pentaciclotienil e indanil urea como abridores de canales de potasio
ES18707374T Active ES2813064T3 (es)	2017-02-28	2018-02-27	Amidas cíclicas como abridores de canales de potasio

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US (2)	US11034665B2 (fr)
EP (3)	EP3366683A1 (fr)
JP (3)	JP6795713B2 (fr)
KR (2)	KR102443685B1 (fr)
CN (2)	CN110312710B (fr)
AU (2)	AU2018227005B2 (fr)
BR (2)	BR122020025103B1 (fr)
CA (2)	CA3238405A1 (fr)
CL (2)	CL2019002445A1 (fr)
CY (2)	CY1123114T1 (fr)
DK (2)	DK3484863T3 (fr)
ES (2)	ES2846772T3 (fr)
HR (2)	HRP20201159T1 (fr)
HU (2)	HUE052703T2 (fr)
IL (1)	IL268931B (fr)
LT (2)	LT3484863T (fr)
MX (2)	MX378574B (fr)
PH (1)	PH12019550146A1 (fr)
PL (2)	PL3567034T3 (fr)
PT (2)	PT3484863T (fr)
RS (2)	RS60648B1 (fr)
SI (2)	SI3567034T1 (fr)
SM (2)	SMT202100053T1 (fr)
WO (1)	WO2018158256A2 (fr)
ZA (1)	ZA201905198B (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP3366683A1 (fr) *	2017-02-28	2018-08-29	Acousia Therapeutics GmbH	Amides, acetamides et ureas cycliques pour ouvris les voies de calcium
JP2023523402A (ja)	2020-04-29	2023-06-05	イドーシアファーマシューティカルズリミテッド	スピロウレア誘導体
EP4172140A1 (fr)	2020-06-25	2023-05-03	Idorsia Pharmaceuticals Ltd	Dérivés de cyclobutyle-urée
CN116600787A (zh) *	2020-11-19	2023-08-15	阿库西亚医疗有限责任公司	非水性凝胶组合物
EP4279061A1 (fr) *	2022-05-18	2023-11-22	Acousia Therapeutics GmbH	Composition de gel aqueux

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH0594034A (ja)	1990-06-29	1993-04-16	Xerox Corp	クラツクのない電子写真画像形成デバイス
ATE228119T1 (de) *	1998-04-15	2002-12-15	Pfizer Prod Inc	Heterocyclische carboxamide
DE19929076A1 (de)	1999-06-25	2000-12-28	Aventis Pharma Gmbh	Indanylsubstituierte Benzolcarbonamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen
DE10061876A1 (de) *	2000-12-12	2002-06-20	Aventis Pharma Gmbh	Arylierte Furan- und Thiophencarbonsäureamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen
AR033095A1 (es)	2001-04-04	2003-12-03	Wyeth Corp	Metodos para el tratamiento de motilidad gastrica hiperactiva
US7273866B2 (en) *	2002-12-20	2007-09-25	Bristol-Myers Squibb Company	2-aryl thiazole derivatives as KCNQ modulators
US7906537B2 (en)	2003-03-21	2011-03-15	H. Lundbeck A/S	Substituted p-diaminobenzene derivatives
TWI349666B (en) *	2004-03-12	2011-10-01	Lundbeck & Co As H	Substituted morpholine and thiomorpholine derivatives
UA89503C2 (uk)	2004-09-13	2010-02-10	Х. Луннбек А/С	Заміщені похідні аніліну
US20060188445A1 (en)	2005-02-22	2006-08-24	Fred Hutchinson Cancer Research Center	Assay for compounds that protect against sensory hair cell death and compounds identified by same
US7790770B2 (en) *	2005-11-23	2010-09-07	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
WO2007087424A2 (fr)	2006-01-25	2007-08-02	The Johns Hopkins University	Procede destine a traiter des troubles lies a kcnq a l’aide de composes organozinc
WO2007138112A2 (fr) *	2006-06-01	2007-12-06	Devgen N.V.	Composés interagissant avec des canaux ioniques, notamment des canaux ioniques de la famille kv
US20090118274A1 (en) *	2007-02-15	2009-05-07	Darin Allen	Monocyclic aminopropyl tetrahydro-pyrazolo-pyridine modulators of cathepsin s
DE102007032436B4 (de)	2007-07-10	2009-07-16	Heraeus Electro-Nite International N.V.	Vorrichtung zum Sammeln von Gasen in Metallschmelzen
US20100256145A1 (en)	2007-08-01	2010-10-07	H. Lundbeck A/S	Use of kcnq potassium channel openers for reducing symptoms of or treating disorders or conditions wherein the dopaminergic system is disrupted
KR20100072077A (ko)	2007-10-17	2010-06-29	사노피-아벤티스	치환된 ｎ페닐비피롤리딘 카복스아미드 및 이의 치료적 용도
CN101896461A (zh) *	2007-12-13	2010-11-24	安姆根有限公司	γ分泌酶调节剂
US7786171B2 (en) *	2008-04-04	2010-08-31	Abbott Laboratories	Amide derivatives as positive allosteric modulators and methods of use thereof
TW201038572A (en)	2009-03-25	2010-11-01	Gruenenthal Gmbh	Substituted spiro-amide compounds
AR078126A1 (es) *	2009-06-04	2011-10-19	Merz Pharma Gmbh & Co Kgaa	Antagonistas de glicina b, composiciones farmaceuticas, usos y proceso de preparacion de los mismos
WO2011085351A2 (fr)	2010-01-11	2011-07-14	The Johns Hopkins University	Procédé de traitement de troubles liés à kcnq
DE102010007281A1 (de)	2010-02-08	2011-08-11	EMC microcollections GmbH, 72070	Neue Aminoalkyl-oxazol- und Aminoalkyl-thiazolcarbonsäureamide und ihre Anwendung zur Stimulation der endogenen situ Regeneration von Haarsinneszellen im Corti'schen Organ des Innenohres beim Säuger
US8586604B2 (en) *	2010-08-20	2013-11-19	Boehringer Ingelheim International Gmbh	Inhibitors of the microsomal prostaglandin E2 synthase-1
TW201217312A (en) *	2010-09-22	2012-05-01	Gruenenthal Gmbh	Substituted benzamide compounds
ES2656972T3 (es) *	2012-02-23	2018-03-01	Vanderbilt University	Análogos de 5-aminotieno [2,3-c] piridazin-6-carboxamida como moduladores alostéricos positivos del receptor de acetilcolina muscarínico M4
DK2900674T3 (en)	2012-09-28	2017-07-03	Univ Washington Through Its Center For Commercialization	RELATIONSHIPS AND PROCEDURES FOR PREVENTION, TREATMENT AND / OR PROTECTION AGAINST SENSITIVE CELL DEATH
WO2014079850A1 (fr)	2012-11-23	2014-05-30	F. Hoffmann-La Roche Ag	Dérivés hétérocycliques substitués
US9572815B2 (en) *	2013-03-15	2017-02-21	St. Jude Children's Research Hospital	Methods and compositions of p27KIP1 transcriptional modulators
PL404138A1 (pl) *	2013-05-31	2014-12-08	Warszawski Uniwersytet Medyczny	Pochodne kwasu benzoesowego jako inhibitory receptora IL-15Rα
US20150126507A1 (en) *	2013-09-05	2015-05-07	Fate Therapeutics, Inc.	Compounds to treat hearing loss
TW201609665A (zh) *	2013-11-05	2016-03-16	赫孚孟拉羅股份公司	作為ＲＯＲｃ調節劑的嗒衍生物
ES2607752T3 (es) *	2013-11-12	2017-04-03	Acousia Therapeutics Gmbh	Compuestos nuevos para regeneración de células y tejidos terminalmente diferenciados
CN105017085B (zh)	2014-04-28	2018-06-29	中国科学院上海药物研究所	一类kcnq钾通道激动剂、其制备方法和用途
WO2016127123A2 (fr) *	2015-02-06	2016-08-11	University Of Washington	Composés et procédés pour prévenir ou traiter la mort de cellules capillaires sensorielles
GB201601301D0 (en) *	2016-01-25	2016-03-09	Takeda Pharmaceutical	Novel compounds
EP3366683A1 (fr)	2017-02-28	2018-08-29	Acousia Therapeutics GmbH	Amides, acetamides et ureas cycliques pour ouvris les voies de calcium

2017
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2018
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Publication number	Publication date
US20200157072A1 (en)	2020-05-21
CN110312710B (zh)	2022-02-15
HUE051854T2 (hu)	2021-03-29
IL268931B (en)	2021-10-31
US20210261518A1 (en)	2021-08-26
AU2018227005A1 (en)	2019-08-22
SI3567034T1 (sl)	2021-03-31
KR20190105058A (ko)	2019-09-11
PH12019550146A1 (en)	2020-06-08
BR122020025103B1 (pt)	2021-06-01
WO2018158256A3 (fr)	2018-12-13
WO2018158256A2 (fr)	2018-09-07
LT3484863T (lt)	2020-07-27
SI3484863T1 (sl)	2020-10-30
KR102443685B1 (ko)	2022-09-15
LT3567034T (lt)	2020-12-10
ES2813064T3 (es)	2021-03-22
AU2021254653B2 (en)	2022-12-08
BR112019017184A2 (pt)	2020-04-28
PL3567034T3 (pl)	2021-05-17
JP7474289B2 (ja)	2024-04-24
US11034665B2 (en)	2021-06-15
MX390303B (es)	2025-03-20
BR112019017184B1 (pt)	2021-06-01
CN114105942B (zh)	2024-07-12
CY1123488T1 (el)	2022-03-24
ZA201905198B (en)	2020-03-25
CA3238405A1 (fr)	2018-09-07
HRP20201159T1 (hr)	2020-11-13
PL3484863T3 (pl)	2020-12-14
RU2020140167A3 (fr)	2021-04-23
DK3484863T3 (da)	2020-09-07
US11884642B2 (en)	2024-01-30
KR20210134826A (ko)	2021-11-10
CL2021001243A1 (es)	2021-10-22
AU2018227005B2 (en)	2021-11-11
SMT202000471T1 (it)	2020-11-10
HRP20201961T1 (hr)	2021-02-05
EP3567034A1 (fr)	2019-11-13
PT3484863T (pt)	2020-08-27
PT3567034T (pt)	2020-12-04
RS61254B1 (sr)	2021-01-29
JP2021008479A (ja)	2021-01-28
JP2022166055A (ja)	2022-11-01
KR102382795B1 (ko)	2022-04-05
EP3484863A2 (fr)	2019-05-22
DK3567034T3 (da)	2021-01-11
EP3567034B1 (fr)	2020-10-28
JP6795713B2 (ja)	2020-12-02
RU2020140167A (ru)	2020-12-16
MX378574B (es)	2025-03-10
CY1123114T1 (el)	2021-10-29
CN110312710A (zh)	2019-10-08
JP2020510694A (ja)	2020-04-09
SMT202100053T1 (it)	2021-03-15
RU2019127116A3 (fr)	2021-03-31
CL2019002445A1 (es)	2020-03-13
AU2021254653A1 (en)	2021-11-18
IL268931A (en)	2019-10-31
CA3052359A1 (fr)	2018-09-07
MX2019010169A (es)	2019-10-21
HUE052703T2 (hu)	2021-05-28
MX2020010866A (es)	2022-02-28
RU2019127116A (ru)	2021-03-30
RS60648B1 (sr)	2020-09-30
EP3366683A1 (fr)	2018-08-29
CN114105942A (zh)	2022-03-01
EP3484863B1 (fr)	2020-06-17

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JP7257367B2 (ja)	2023-04-13	聴覚損失の予防および治療のための方法および組成物
AU2016301282A1 (en)	2018-03-29	Charged ion channel blockers and methods for use
Cousins	2022	Hearing loss drug discovery and medicinal chemistry: current status, challenges, and opportunities
US7696197B2 (en)	2010-04-13	Use of a phenothiazine derivative for preventing and/or treating hearing loss
RU2779131C2 (ru)	2022-09-01	Новые соединения, используемые в качестве открывателей калиевых каналов
RU2779111C2 (ru)	2022-08-31	Новые соединения, используемые в качестве открывателей калиевых каналов
NZ792296A (en)	2025-01-31	Novel compounds useful as potassium channel openers